Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Compared to heavy drinking and abstinence, a moderate consumption of alcohol is associated with lower mortality rates due to coronary heart disease. About half of the protective effect of alcohol on cardiovascular risk can be explained by its ability to raise HDL-cholesterol. Alcohol can influence HDL metabolism at more than one site. Since light-to-moderate alcohol intake is associated with enhanced insulin sensitivity and improvement of insulin sensitivity results in higher HDL-cholesterol levels, it is suggested that this is one of the routes taken by alcohol to act upon HDL metabolism. Whether interrelated or not, both the HDL-cholesterol increase and enhanced insulin sensitivity are considered to have a beneficial effect on the process of atherosclerosis. Because of the well-known adverse consequences of excess alcohol use, these facts have not changed public health policy. On the other hand, they may have an impact on advice to selected patients, diabetics or non-diabetics.
 ...
PMID:Alcohol and insulin sensitivity. 959 64

As reviewed in the Part I companion manuscript by Basavaraju and Jones (Arch Environ Contam Toxicol), atherosclerosis and carcinogenesis may share some common mechanisms of toxicological action. On that hypothesis, standardized test data taken from the Registry of Toxic Effects of Chemical Substances (RTECS) were used to compute relative potency factors for chemical compounds associated with increased risk of atherosclerosis to humans. Potencies of the different compounds were computed relative to each of six reference compounds comprised of benzo(a)pyrene, nicotine, cisplatin, adriamycin, estrogen, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Reference-specific potencies were all converted to a common numerical scale adjusted to unit potency for B(a)P. Because the list of compounds contained several antibiotics, amino acids, hormones, chemotherapeutic agents, polynuclear aromatics, alkaloids, metals, and vitamins, the standardized estimates of potency varied significantly depending on which of the six reference compounds are considered as standards of comparison. For the n - 1 other substances. Estimates of relative potency, risk coefficients, and generalized risk equations are estimated for cigarette smoke condensate, dietary cholesterol, ethanol, and carbon disulfide. From data on atherosclerosis as a result of cigarette smoking, a tentative risk was estimated as Increased Relative Risk = S (mg/kg-day)-1 x dose (mg/kg-day) x RP, where the dose is chronic intake per kilogram of body weight per day, RP is the potency of the compound of interest relative to that of benzo(a)pyrene, and S is 0.83, 0.25, 0.20, or 13 depending on whether cigarette smoke, cholesterol, ethanol, or carbon disulfide epidemiological data were used as a standard of comparison.
 ...
PMID:Atherosclerotic risks from chemicals: part II. A RASH analysis of in vitro and in vivo bioassay data to evaluate 45 potentially hazardous compounds. 960 35

Many epidemiological studies have shown that moderate alcohol intake, from 10 to 30 g of ethanol a day, decreases cardiovascular mortality from atherosclerotic ischaemic heart disease and ischaemic stroke as compared to non-drinkers. This beneficial effect outweighs the risks of alcohol consumption in subgroups of people with a higher risk of atherosclerosis: the elderly, people with coronary risk factors and patients with previous coronary events. It has not been demonstrated that alcohol intake, even in moderate amounts, is beneficial for the general population, in particular, men under the age of 40 and women under 50, because it raises mortality due to other causes, especially injury, cirrhosis of the liver and some types of cancer, thereby outweighing the benefits for coronary artery disease. Thus, alcohol consumption should not be recommended as a prophylaxis for the general population. Guidelines on alcohol drinking habits--whether to continue, to start, to modify or to stop--must be given on an individual basis, taking into account the relative risks and benefits for each patient. The benefits of moderate alcohol consumption on the cardiovascular system seem to be exerted fundamentally through its effects on plasma lipoproteins, principally by raising high density lipoprotein (HDL) cholesterol and to a lesser degree, by decreasing low density lipoprotein (LDL) cholesterol. It appears to exert additional beneficial effects on the heart by decreasing platelet aggregability and by bringing about changes in the clotting-fibrinolysis system. Although there has been some debate about the relative superiority of different types of alcoholic beverages (wine, beer or hard liquor), and to a greater extent, about different types of wine, there is no current evidence of any kind of beneficial effect from other components of the beverage besides ethanol. Thus, it does not seem appropriate to recommend any particular type of alcoholic drink, except for sociocultural reasons. The added benefits from some components of different types of wine with a high antioxidant activity on plasma lipoproteins remain only an interesting hypothesis. Meanwhile, encouraging a healthy diet, flavonoid rich and with a predominance of natural ingredients (fruit, legumes, cereals and seeds), in the general population should stop the current tendency of Southern European countries from abandoning the Mediterranean diet. Because of the multifactorial nature of coronary heart disease, it is necessary to remember that atherosclerotic risk reduction is achieved by behavior modification of multiple risk factors present in individual patients and in the general population. Therefore, guidelines regarding alcohol intake should always be linked to pertinent recommendations about other atherosclerotic risk factors.
 ...
PMID:[Wine and heart]. 1021 74

Alcoholic fatty liver and hyperlipemia result from the interaction of ethanol and its oxidation products with hepatic lipid metabolism. An early target of ethanol toxicity is mitochondrial fatty acid oxidation. Acetaldehyde and reactive oxygen species have been incriminated in the pathogenesis of the mitochondrial injury. Microsomal changes offset deleterious accumulation of fatty acids, leading to enhanced formation of triacylglycerols, which are partly secreted into the plasma and partly accumulate in the liver. However, this compensatory mechanism fades with progression of the liver injury, whereas the production of toxic metabolites increases, exacerbating the lesions and promoting fibrogenesis. The early presence of these changes confers to the fatty liver a worse prognosis than previously thought. Alcoholic hyperlipemia results primarily from increased hepatic secretion of very-low-density lipoprotein and secondarily from impairment in the removal of triacylglycerol-rich lipoproteins from the plasma. Hyperlipemia tends to disappear because of enhanced lipolytic activity and aggravation of the liver injury. With moderate alcohol consumption, the increase in high-density lipoprotein becomes the predominant feature. Its mechanism is multifactorial (increased hepatic secretion and increased extrahepatic formation as well as decreased removal) and explains part of the enhanced cholesterol transport from tissues to bile. These changes contribute to, but do not fully account for, the effects on atherosclerosis and/or coronary heart disease attributed to moderate drinking.
Recent Dev Alcohol 1998
PMID:Alcohol and lipids. 975 44

The ingestion of one or two alcoholic drinks can affect heart rate, blood pressure, cardiac output, myocardial contractility, and regional blood flow. These actions generally are not clinically important. In the presence of cardiovascular disease, however, even such small quantities of alcohol might result in transient unfavorable hemodynamic changes. Moreover, alcohol abuse can produce cardiac arrhythmias, hypertension, cardiomyopathy, stroke, and even sudden death. In contrast, moderate alcohol use produces changes that have an overall favorable effect on atherosclerotic-related vascular diseases. Because cardiovascular disease due to atherosclerosis is the leading cause of death in Western society, this desirable effect of alcohol use outweighs its detrimental actions, resulting in favorable findings in population studies. Nevertheless, the body of evidence argues against encouraging alcohol use for its cardiovascular effects.
Recent Dev Alcohol 1998
PMID:Cardiovascular effects of alcohol. 975 45

The aim of the study was to investigate in a population-based series (1031 subjects, age range 40-60 years) whether the renal size of hypertensive subjects differs from that of control subjects and whether the difference might be due to hypertension itself or risk factors associated with hypertension. The renal measurements were performed by abdominal ultrasound. The genders were analyzed separately. Hypertensive men had slightly larger kidneys than controls (70.1+/-8.9 cm2 vs. 67.9+/-8.7 cm2, p <0.008). The difference was, however, mediated mainly through the body mass index (BMI), whereas hypertension, blood pressure or hypertensive medication did not affect renal size. High serum concentrations of uric acid and creatinine were associated with smaller kidney size (p <0.001 and p <0.05, respectively). Alcohol users had slightly larger kidneys than abstainers, but the difference was not significant. Renal size increased with pack years of smoking. Diabetics had 4.8% larger kidneys (p <0.039), but no difference was observed between the subjects with impaired glucose tolerance and those with normal test results. In multivariate analysis, the most significant factors associated with enlarged kidney size were the fasting blood glucose concentration (p < or = 0.0001), smoking (p < or = 0.0001) and atherosclerotic lesions in carotid arteries (p <0.002). The kidneys were also slightly larger in hypertensive women than in control subjects, but the difference was only of borderline significance (p <0.08). Women on hormone replacement therapy had smaller kidneys than other women (p <0.05), but there was no difference in renal measures between premenopausal and postmenopausal women. In multivariate analysis, the most significant factors contributing to large kidney size were blood glucose concentration (p <0.0001) and smoking (p <0.05), while age and serum creatinine concentration were associated with smaller kidney size (p <0.0001 and p <0.0001). We conclude that renal size is related to sex and the subject's height and weight. Smoking, abnormal glucose tolerance, blood uric acid, creatinine, carotid atherosclerosis and hormone replacement therapy in women were also significant factors for renal size. Hypertensive subjects had larger kidneys than controls, mainly because of their more frequent obesity and abnormal glucose test.
 ...
PMID:Effect of hypertension, diabetes and other cardiovascular risk factors on kidney size in middle-aged adults. 977 19

Atherosclerosis is a vascular injury characterized by elevated tissue levels of tumor necrosis factor-alpha (TNF-alpha), increased expression of endothelial cell adhesion molecules, and vascular wall inflammatory cell infiltration. Foam cells are associated with atherosclerotic plaque material, and low density lipoprotein (LDL) is a lipid component of foam cells. Malondialdehyde (MDA) is an oxidative product of unsaturated fatty acids and is also present in atherosclerotic lesions. MDA-modified (adducted) proteins, including MDA-modified LDL, are present in atherosclerotic human vascular tissue. Acetaldehyde (AA) is the major metabolic product of ethanol oxidation. Both MDA and AA are highly reactive aldehydes and will combine with proteins to produce an antigenically distinct protein adduct, termed the MAA adduct. This study demonstrates that proteins modified in the presence of high concentrations of MDA can produce MAA-modified proteins in vitro. In addition, MAA adducted proteins are capable of inducing rat heart endothelial cell cultures (rHEC) to produce and release TNF-alpha, and cause rHEC upregulation of endothelial adhesion molecule expression, including ICAM-1. These adhesion molecules are required for circulating inflammatory cells to adhere to endothelium which allows inflammatory cell tissue infiltration. Additionally, MAA modified proteins were defected in human atherosclerotic aortic vascular tissue but not in normal aortic tissue. Since atherosclerosis is associated with an inflammatory vascular injury characterized by elevated tissue TNF-alpha concentrations and inflammatory cell infiltration, these data suggest that MAA-adducted proteins may be formed in atherosclerotic plaque material and may be involved in the inflammatory reaction that occurs in atherosclerosis. These data further suggest that previous studies demonstrating MDA modified protein in atherosclerotic plaque may in fact have MAA modified proteins associated with them.
Atherosclerosis 1998 Nov
PMID:Association of malondialdehyde-acetaldehyde (MAA) adducted proteins with atherosclerotic-induced vascular inflammatory injury. 986 43

Rats were fed diets containing different ratios of linoleate (18:2 n-6) to alpha-linolenate (18:3 n-3), and the severity of gastric injury induced by ethanol, ischemia/reperfusion and water-immersion stress was compared. On decreasing the 18:2 n-6/18:3 n-3 ratios in the diets, the proportion of arachidonic acid (20:4 n-6) decreased and that of eicosapentaenoic acid (20:5 n-3) increased in the phospholipids of the gastric mucosa, which was associated with decreased mucosal prostaglandin E2 content. Mucosal injury in all the three experimental models was exacerbated significantly in the diet group fed 18:2 n-6/18:3 n-3 ratio of 0.25 (perilla oil) as compared with the groups fed dietary oils with 18:2 n-6/18:3 n-3 ratios of 2.7 (mixture of perilla and safflower oils) and 127 (safflower oil). This adverse effect induced by perilla oil diet was not observed when rats were pretreated with a mild irritant (20% ethanol) prior to challenge with a strong irritant (absolute ethanol). Furthermore, an 18:2 n-6/18:3 n-3 ratio of as low as 1 was found to be in a safe range in the water-immersion stress ulcer model. Thus, oils with very low n-6/n-3 ratios, for example perilla oil, could be used without the risk of the observed adverse effects on experimental gastric injury in people of industrialized countries ingesting foods with n-6/n-3 ratios of above 4. A decrease in the n-6/n-3 ratios to 2 or below is still recommended for the prevention of chronic diseases in the elderly related to atherosclerosis and inflammation.
 ...
PMID:Effect of dietary linoleate/alpha-linolenate balance on experimentally induced gastric injury in rats. 988 6

Serum or plasma levels of Lp(a) vary widely between individuals and are higher in Africans and their descendants compared with white persons. In whites, high serum levels of Lp(a) are associated with the premature development of atherosclerosis. In both ethnic groups, serum Lp(a) levels are highly genetically determined and only a few environmental or physiological factors, like testosterone or estrogen, have been shown to lower serum Lp(a) levels. In whites, alcohol consumption is associated with lower serum Lp(a) levels. However, the mechanism underlying this association and whether it holds true for blacks is not known. To address these questions, we analyzed serum Lp(a) levels in 333 middle-aged males of African descent from the Seychelles Islands (Indian Ocean). In addition, we analyzed the size of the apo(a) isoforms and the serum levels of albumin and sex hormones in a subset of 279 subjects. Serum Lp(a) levels were similar in teetotalers (median, 32.5 mg/dL; n=42) and occasional drinkers (median, 34.1 mg/dL; n=112). In contrast, individuals consuming 10 to 80 g of ethanol/d (n=83) and heavy drinkers (>80 g of ethanol/d, n=96) had a 9% and 32% lower median Lp(a) level than teetotalers, respectively (P=0.01). The size distribution of the apo(a) isoforms and the mean serum levels of albumin, estradiol, and luteinizing hormone were similar in teetotalers and occasional drinkers compared with moderate and heavy drinkers. These latter 2 groups had lower serum levels of testosterone and sex hormone-binding globulin. These data indicate that alcohol intake is associated in a dose-dependent manner with lower serum Lp(a) levels in males of African descent and that this association is not related to the size of the apo(a) isoforms, to the synthetic function of the liver, or to sex hormone biochemical status.
 ...
PMID:Dose-dependent inverse relationship between alcohol consumption and serum Lp(a) levels in black African males. 1019 38

Alcohol taken in moderation may prevent atherosclerosis, whereas heavy drinking has the opposite effect, in part by promoting oxidation of low density lipoproteins (LDL), a pathogenetic factor in atherogenesis. We assess here: 1 ) whether similar alterations can be reproduced in baboons fed 50% of energy as ethanol (the average intake of alcoholics) for 7- 8 years, and 2 ) whether such alterations are affected by supplementation with polyenylphosphatidylcholine (PPC), a mixture of polyunsaturated phosphatidylcholines, shown to prevent alcoholic fatty liver, fibrosis, and cirrhosis. Ten animals were given the ethanol-containing diet and ten were pair-fed isocaloric control diets. In half of the pairs, the diets were supplemented with 2.8 g of polyenylphosphatidylcholine/1000 kcal. Alcohol feeding increased LDL-lipoperoxides and made LDL-proteins more negatively charged, changes that were attenuated or prevented by PPC. The oxidizability of LDL was determined in vitro by the formation of conjugated dienes after oxidation with copper. Alcohol shortened the lag time (which measures LDL antioxidant capacity); this effect was normalized by PPC supplementation. By contrast, PPC produced no changes in the controls. Thus polyenylphosphatidylcholine, by markedly attenuating the ethanol-induced increase in LDL oxidation, opposes one of the effects whereby alcohol promotes atherosclerosis.
 ...
PMID:Oxidation of LDL in baboons is increased by alcohol and attenuated by polyenylphosphatidylcholine. 1035 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>